Our study implied that the therapeutic silencing of SMOC2 can improve ISO-induced myocardial fibrosis and heart function reduction in vivo, and ameliorate proliferation and collagen deposition of CFs induced by TGFβ in vitro, and the down-regulation of ILK/p38 may be the underlying mechanism. Here, TGFB1 is linked to Myocardial fibrosis.